A study of intestinal mucosal function in the piebald mouse model for congenital aganglionic megacolon is proposed. The principal aims of the study are twofold. The first is to characterize intestinal mucosal function in normal mice and to identify alterations in intestinal function that occur in their siblings with congenital megacolon. The second is to elucidate the mechanisms involved in the compensatory changes in mucosal function that occur in megacolonic mice. The proposed experiments are designed to investigate the involvement of the following factors in the known compensatory changes in mucosal function of the megacolonic mouse model: (1) mucosal permeability changes, (2) alteration of sodium-potassium ATPase in the basolateral membrane, (3) trophic changes in the mucosa, (4) morphometric changes in the mucosa, (5) intramural nerve elements, and (6) gastrointestinal transit time. The proposed project would provide new insight into mechanisms that underlie alterations in intestinal function in Hirschsprung's disease and other forms of distal intestinal obstruction. Mucosal transport function in the jejunum has not been studied as extensively as the ileal and colonic mucosa, and a secondary benefit of the project would be to fill gaps in existing knowledge of jejunal transport mechanisms.